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Clinical Trial Record

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A Phase I/II Study of OBI-3424 in Subjects with Advanced Solid Tumors

2018-07-02

2024-02-13

2024-03-21

68

Study Overview

A Phase I/II Study of OBI-3424 in Subjects with Advanced Solid Tumors

A first-in-human open-label, Phase I/II study to evaluate the safety, tolerability, MTD/RP2D, PK, and preliminary efficacy of OBI-3424 administered as a single agent.

N/A

  • Solid Tumor
  • Pancreatic Adenocarcinoma
  • DRUG: OBI-3424
  • OBI-3424-001

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates Results Reporting Dates Study Record Updates

2018-05-21  

N/A  

2024-10-11  

2018-07-09  

N/A  

2024-10-15  

2018-07-19  

N/A  

2024-04  

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: Dose escalation phase

OBI-3424 (1.0 mg/m^2 to 14.0 mg/m^2) will be administered by IV infusion on Days 1 and 8 of each 21-day cycle or Day 1 of each 21-day cycle to determine the MTD and RP2D with a classic 3+3 dose escalation design.

DRUG: OBI-3424

  • liquid formulation for Intravenous infusion
EXPERIMENTAL: Cohort expansion phase

OBI-3424 (12 mg/m^2) will be administered by IV infusion on Day 1 of each 21-day cycle.

DRUG: OBI-3424

  • liquid formulation for Intravenous infusion
Primary Outcome MeasuresMeasure DescriptionTime Frame
Incidence and severity of adverse events (AEs)Adverse events will be graded according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.Adverse events will be noted as it occurs. Timeframe for measure begins after first administration of study drug until 30 days after last dose of study drug. Study duration defined as up to 2 years from the first dose.
Assess safety changes in electrocardiogram (ECG)Resting 12-lead ECGs will be obtained from all subjects' pre-OBI-3424 infusion and within 15 minutes post-OBI-3424 infusion in order to assess any impact OBI-3424 may have on the QT interval as assessed by the Fridericia's Correction Formula (QTcF).Day 1 Cycles 1 and 2 (each cycle is 21 days)
Assess safety changes of body weight.If during treatment a subject's body weight changes by >10%, the dose should be adjusted.Day 1 of each cycle (there are 34 cycles; 21 days for each cycle)
Number of participants with dose limiting toxicities (DLTs)A DLT is defined as the occurrence of Grade 3/4 adverse events within the first cycle (the first 21 days) of treatment that are considered by the investigator to be at least possibly related to OBI-3424.Throughout Cycle 1 (21 days for each cycle)
Define the Recommended Phase 2 Dose (RP2D)Determination of the MTD, based on the frequently of DLTs observed in Cycle 1 in subjects recruited to the Dose Escalation Phase.Days 1 and 8 of each cycle (all 34 cycles and there are 21 days for each cycle)
Pharmacokinetics (PK) - Time to maximum concentration (Tmax)Tmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)
PK - Maximum peak plasma concentration (Cmax)Cmax of OBI-3424 and OBI-2660 will be computed for each subject where possible.Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)
PK - The magnitude of the slope of the linear regression of the log concentration vs. time profile during the terminal phase (Kel)Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)
PK - Half-life (T1/2)T1/2 computed as ln (2)/Kel of OBI-3424 and OBI-2660 will be computed for each subject where possible.Days 1 and 8 of Cycle 1 (first cycle of 34 cycles and there are 21 days for each cycle)
PK - Area under the concentration-time curve (AUClast)AUClast from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawnDays 1 and 8 of Cycle 1 (Cycle 1 is 21 days)
Secondary Outcome MeasuresMeasure DescriptionTime Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

    Inclusion Criteria (all subjects):
    1. At least 18 years of age 2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 3. Recovered from toxicities of prior therapy to Grade 0 or 1 4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) criteria 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Acceptable liver function:
    1. Bilirubin ≤1.5 × institutional ULN 2. AST and ALT ≤3.0 × ULN, or ≤5.0 × ULN for subjects with liver involvement 7. Acceptable renal function:
    a. Creatinine clearance >30 mL/min according to the Cockcroft-Gault formula 8. Acceptable hematologic status (without hematologic support, other than red blood cell transfusion):
    1. ANC ≥1500 cells/μL 2. Platelet count ≥100,000/μL 3. Hemoglobin ≥9.0 g/dL (prior packed red blood cell transfusion or erythropoietin support is allowed). 9. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation.
    Dose Escalation Phase Subjects Only (Inclusion Criteria): 10. Histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective 11. Tumor progression after most recent therapy
    Expansion Phase Subjects Only (Inclusion Criteria): 12. Available tumor tissue, either archival or fresh (fresh preferred). 13. For treatment, an AKR1C3 IHC H-score of ≥ 100 using a validated IHC assay in one of the following tumor types to be enrolled in the respective cohort:
    1. Cohort A: Pancreatic Adenocarcinoma 2. Cohort B: Basket (any solid tumor type other than pancreatic adenocarcinoma)
    Exclusion Criteria:
    1. Prior radiotherapy to more than 25% of the bone marrow 2. Symptomatic brain metastases, unless previously treated and well controlled for at least 4 weeks after central nervous system (CNS)-directed treatment as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the Screening Period. Patients with known leptomeningeal disease are excluded. 3. Previously treated malignancies, except for adequately treated non-melanoma skin cancer, in situ cancer, or other cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the current study 4. Patients with hepatocellular carcinoma (applies to Expansion Phase only) 5. Major surgery, other than diagnostic surgery, within 4 weeks prior to Day 1, without complete recovery 6. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy 7. Treatment with radiation therapy, surgery, chemotherapy, targeted therapies or hormones within 3 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C) 8. Concomitant use of strong CYP3A4 inhibitors/inducers 9. Concomitant use of naproxen within a 48-hour window before and after OBI-3424 dosing 10. Females who are pregnant or breast-feeding 11. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study 12. Unwillingness or inability to comply with the study protocol for any reason

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

    • PRINCIPAL_INVESTIGATOR: Apostolia Tsimberidou, MD, PHD, M.D. Anderson Cancer Center

    Publications

    The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

    General Publications

    • Tsimberidou AM, Verschraegen CF, Wesolowski R, Shia CS, Hsu P, Pearce TE. Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, and clinical activity of OBI-3424 in patients with advanced or metastatic solid tumors. Br J Cancer. 2023 Aug;129(2):266-274. doi: 10.1038/s41416-023-02280-4. Epub 2023 May 12.
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